Nanotechnology is rapidly entering the therapeutics of human disease with novel drug delivery and targeting systems for increased specificity. In the newly defined area of nanomedicine, nanotechnology will provide innovative diagnostic/therapeutic approaches to human diseases. In regards to cancer therapy, Photodynamic therapy (PDT) is rapidly maturing as a standard treatment for many types of cancers. This proposal focuses on the integration of nanotechnology into photodynamic therapeutic approaches. First, we propose to investigate the use of upconversion nanophosphor technology to excite, in situ, photosensitizers (nanophosphor-PDT). Second, we propose to use nanoencapsulation techniques for the better delivery, targeting and effectiveness of hydrophobic photosensitizers. Nanophosphors are rare earth ion nanoparticles that convert infrared light (974 nm) to visible light. Coupled with the appropriate photosensitizing agent, these nanophosphors can provide in situ activation of these agents. Nanoencapsulation will enhance the efficacy of the hydrophobic agents by providing a non-aggregating formula of the agent thereby increasing the phototoxicity due to less aggregation and photodegradation. A multidisciplinary program will be involved in the integration of the nanotechnology approaches for PDT proposed in this application. In the development of this concept, we propose to use nanotechnology to provide new approaches for the treatment of neoplastic disease using new and established photosensitizers in mammalian disease systems. New therapeutic nanotechnological approaches will be accomplished in the following approaches: 1) Nanophosphor generation of light within the tissue (in situ) and cells using upconverting nanophosphor articles; 2) Development of photosensitizer encapsulated in organically modified silica nanoparticles as an, effective mechanism for delivery of these hydrophobic agents; and 3) Integration of these two nanotechnologies by their fusion into composite and conjugated nanoparticles. Each approach will be individually evaluated, in vitro and in vivo, for therapeutic efficacy using established techniques.